Sodium Hydroxide → HCID 59635334, compound

HRID 2191214Notes

Reaction equation

HRID 2191214 reaction equation
COC([N:5]1[C:11]2[C:12]([CH3:17])=[CH:13][C:14]([CH3:16])=[CH:15][C:10]=2[C@@H:9]([NH:18][C:19]2[N:20]=[N:21][N:22]([CH3:24])[N:23]=2)[CH2:8][CH2:7][CH2:6]1)=O.[OH-].[Na+]>C(O)C>[CH3:16][C:14]1[CH:13]=[C:12]([CH3:17])[C:11]2[NH:5][CH2:6][CH2:7][CH2:8][C@H:9]([NH:18][C:19]3[N:20]=[N:21][N:22]([CH3:24])[N:23]=3)[C:10]=2[CH:15]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 596353361H-1-Benzazepine-1-carboxylic acid, 2,3,4,5-tetrahydro-7,9-dimethyl-5-[(2-methyl-2H-tetrazol-5-yl)amino]-, methyl ester, (5S)-

Product 1

HCID 59635334HCID 59635334, compoundYield 84.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

Combine methyl-(5S)-7,9-dimethyl-5-[(2-methyl-2H-tetrazol-5-yl)amino]-2,3,4,5-tetrahydro-1H-1-benzazepine-1-carboxylate (20.1 g), NaOH (12.10 g), and ethanol (80 mL) in a 250 mL teflon flask with overhead stirring. Sparge with nitrogen for 10 minutes, heat to reflux (85° C.) for ˜5.5 hours. Cool to room temperature with a cool water bath. Add acetic acid/water (17.5 mL/53 mL) slowly at room temperature and transfer to 500 mL flask about half way through addition (−30 min total time for addition). Seed with ˜5 mg of (5S)-7,9-dimethyl-N-(2-methyltetrazol-5-yl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-amine Heat to 50° C. (up to temperature in about 15 minutes). Add 54 mL of water over about 30 minutes. The next day, cool in ice bath, filter and rinse with methanol:water (1:1; 2×30 mL). Dry wet cake in vacuo at 60° C. to yield 13.99 g of (5S)-7,9-dimethyl-N-(2-methyltetrazol-5-yl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-amine HPLC analysis: 99.4%, ret time is 4.84 min. Chiral HPLC: 98.5% chiral purity.

Workup

  1. customSparge with nitrogen for 10 minutes
  2. temperatureheat
  3. temperatureCool to room temperature with a cool water bath
  4. additionAdd acetic acid/water (17.5 mL/53 mL) slowly at room temperature and transfer to 500 mL flask about half way through addition (−30 min total time for addition)
  5. temperatureSeed with ˜5 mg of (5S)-7,9-dimethyl-N-(2-methyltetrazol-5-yl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-amine Heat to 50° C. (up to temperature in about 15 minutes)
  6. additionAdd 54 mL of water over about 30 minutes
  7. temperatureThe next day, cool in ice bath
  8. filtrationfilter
  9. washrinse with methanol:water (1:1; 2×30 mL)
  10. customDry wet cake in vacuo at 60° C.

Sources & evidence

ORD record
ord-002e5f5efc6540d8bafd41c2bc5d244b
Source dataset
uspto-grants-2012_12
Patent number
US08329688B2

Reaction notes

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